| 1. |
- Arndt, D. S., et al.
(författare)
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STATE OF THE CLIMATE IN 2017
- 2018
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Ingår i: Bulletin of The American Meteorological Society - (BAMS). - : American Meteorological Society. - 0003-0007 .- 1520-0477. ; 99:8, s. S1-S310
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Forskningsöversikt (refereegranskat)
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| 2. |
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| 3. |
- Helbig, K. L., et al.
(författare)
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De Novo Pathogenic Variants in CACNA1E Cause Developmental and Epileptic Encephalopathy with Contractures, Macrocephaly, and Dyskinesias
- 2018
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Ingår i: American Journal of Human Genetics. - : Elsevier BV. - 0002-9297 .- 1537-6605. ; 103:5, s. 666-678
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Tidskriftsartikel (refereegranskat)abstract
- Developmental and epileptic encephalopathies (DEEs) are severe neurodevelopmental disorders often beginning in infancy or early childhood that are characterized by intractable seizures, abundant epileptiform activity on EEG, and developmental impairment or regression. CACNA1E is highly expressed in the central nervous system and encodes the alpha(1)-subunit of the voltage-gated Ca(V)2.3 channel, which conducts high voltage-activated R-type calcium currents that initiate synaptic transmission. Using next-generation sequencing techniques, we identified de novo CACNA1E variants in 30 individuals with DEE, characterized by refractory infantile-onset seizures, severe hypotonia, and profound developmental impairment, often with congenital contractures, macrocephaly, hyperkinetic movement disorders, and early death. Most of the 14, partially recurring, variants cluster within the cytoplasmic ends of all four S6 segments, which form the presumed Ca(V)2.3 channel activation gate. Functional analysis of several S6 variants revealed consistent gain-of-function effects comprising facilitated voltage-dependent activation and slowed inactivation. Another variant located in the domain II S4-S5 linker results in facilitated activation and increased current density. Five participants achieved seizure freedom on the anti-epileptic drug topiramate, which blocks R-type calcium channels. We establish pathogenic variants in CACNA1E as a cause of DEEs and suggest facilitated R-type calcium currents as a disease mechanism for human epilepsy and developmental disorders.
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| 4. |
- Smol, T., et al.
(författare)
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MED13L-related intellectual disability: involvement of missense variants and delineation of the phenotype
- 2018
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Ingår i: Neurogenetics. - : SPRINGER. - 1364-6745 .- 1364-6753. ; 19:2, s. 93-103
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Tidskriftsartikel (refereegranskat)abstract
- Molecular anomalies in MED13L, leading to haploinsufficiency, have been reported in patients with moderate to severe intellectual disability (ID) and distinct facial features, with or without congenital heart defects. Phenotype of the patients was referred to "MED13L haploinsufficiency syndrome." Missense variants in MED13L were already previously described to cause the MED13L-related syndrome, but only in a limited number of patients. Here we report 36 patients with MED13L molecular anomaly, recruited through an international collaboration between centers of expertise for developmental anomalies. All patients presented with intellectual disability and severe language impairment. Hypotonia, ataxia, and recognizable facial gestalt were frequent findings, but not congenital heart defects. We identified seven de novo missense variations, in addition to protein-truncating variants and intragenic deletions. Missense variants clustered in two mutation hot-spots, i.e., exons 15-17 and 25-31. We found that patients carrying missense mutations had more frequently epilepsy and showed a more severe phenotype. This study ascertains missense variations in MED13L as a cause for MED13L-related intellectual disability and improves the clinical delineation of the condition.
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| 5. |
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| 6. |
- McGinn, Steven, et al.
(författare)
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New Technologies for DNA analysis-A review of the READNA Project.
- 2016
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Ingår i: New Biotechnology. - : Elsevier BV. - 1876-4347 .- 1871-6784.
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Forskningsöversikt (refereegranskat)abstract
- The REvolutionary Approaches and Devices for Nucleic Acid analysis (READNA) project received funding from the European Commission for 4 1/2 years. The objectives of the project revolved around technological developments in nucleic acid analysis. The project partners have discovered, created and developed a huge body of insights into nucleic acid analysis, ranging from improvements and implementation of current technologies to the most promising sequencing technologies that constitute a 3(rd) and 4(th) generation of sequencing methods with nanopores and in situ sequencing, respectively.
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| 7. |
- Robson, Harry K., et al.
(författare)
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Carbon and nitrogen stable isotope values in freshwater, brackish and marine fish bone collagen from Mesolithic and Neolithic sites in central and northern Europe
- 2016
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Ingår i: Environmental Archaeology. - 1461-4103. ; 21:2, s. 105-118
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Tidskriftsartikel (refereegranskat)abstract
- The aim of this research is to examine the isotopic characterisation of archaeological fish species as it relates to freshwater, brackish and marine environments, trophic level and migration patterns, and to determine intraspecies variation within and between fish populations in different locations within central and northern Europe. Carbon and nitrogen stable isotope analysis was undertaken on collagen extracted from 72 fish bone samples from eight Mesolithic and Neolithic archaeological sites in this region. Thirty-six (50%) of the specimens analysed produced results with acceptable carbon to nitrogen atomic ratios (2·9–3·6). The fish remains encompassed a wide spectrum of freshwater, brackish and marine taxa (n = 12), which were reflected in the δ13C values (−24·5 to −7·8‰). The freshwater/brackish fish (pike, Esox lucius; perch, Perca fluviatilis; zander, Sander lucioperca) had δ13C values that ranged from −24·2 to −19·3‰, whereas the brackish/marine fish (spurdog, Squalus acanthias; flatfish, Pleuronectidae; codfish, Gadidae; garfish, Belone belone; mackerel, Scomber scombrus) ranged from −14·9 to −9·4‰. Salmonidae, an anadromous taxon, and eel (Anguilla anguilla), a catadromous species, had carbon isotope values consistent with marine origin, and no evidence of freshwater residency (−12·7 to −11·7‰). The δ15N values had a range of 6·2‰ (6·5–12·7‰) indicating that these fish were on average feeding at 1·7 trophic levels higher than their producers in these diverse aquatic environments. These results serve as an important ecological baseline for the future isotopic reconstruction of the diet of human populations dating to the late Mesolithic and early Neolithic of the region.
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| 8. |
- Singh-Bhalla, Guneeta, et al.
(författare)
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Unexpected termination switching and polarity compensation in LaAlO3/SrTiO3 heterostructures
- 2018
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Ingår i: Physical Review Materials. - : AMER PHYSICAL SOC. - 2475-9953. ; 2:11
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Tidskriftsartikel (refereegranskat)abstract
- Polar crystals composed of charged ionic planes cannot exist in nature without acquiring surface changes to balance an ever-growing dipole. The necessary changes can manifest structurally or electronically as observed in semiconductors and ferroelectric materials through screening charges and/or domain wall formation. In the case of prototypical polar complex oxides such as the LaAlO3/SrTiO3 system the nature of screening charges for different interface terminations is not symmetric. Electron accumulation is observed near the LaAlO3/TiO2-SrTiO3 interface, while the LaAlO3/SrO-SrTiO3 stack is insulating. Here, we observe evidence for an asymmetry in the surface chemical termination for nominally stoichiometric LaAlO3 films in contact with the two different surface layers of SrTiO3 crystals, TiO2 and SrO. Using several element-specific probes, we find that the surface termination of LaAlO3 remains AlO2 irrespective of the starting termination of SrTiO3 substrate surface. We use a combination of cross-plane tunneling measurements and first-principles calculations to understand the effects of this unexpected termination on band alignments and polarity compensation of LaAlO3/SrTiO3 heterostructures. An asymmetry in LaAlO3 polarity compensation and resulting electronic properties will fundamentally limit atomic level control of oxide heterostructures.
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